DHB4_DROME
ID DHB4_DROME Reviewed; 598 AA.
AC Q9VXJ0;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Peroxisomal multifunctional enzyme type 2 {ECO:0000303|PubMed:21320074};
DE Short=DmMFE-2 {ECO:0000303|PubMed:21320074};
DE Includes:
DE RecName: Full=(3R)-hydroxyacyl-CoA dehydrogenase {ECO:0000303|PubMed:21320074};
DE EC=1.1.1.n12 {ECO:0000269|PubMed:21320074};
DE Includes:
DE RecName: Full=Enoyl-CoA hydratase 2 {ECO:0000303|PubMed:21320074};
DE EC=4.2.1.119 {ECO:0000269|PubMed:21320074};
GN Name=Mfe2 {ECO:0000312|FlyBase:FBgn0030731}; ORFNames=CG3415;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1] {ECO:0000312|EMBL:AAF48572.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAF48572.1}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAK92917.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569};
RC TISSUE=Head {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000305, ECO:0000312|PDB:3OML}
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH NAD, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=21320074; DOI=10.1042/bj20101661;
RA Haataja T.J., Koski M.K., Hiltunen J.K., Glumoff T.;
RT "Peroxisomal multifunctional enzyme type 2 from the fruitfly: dehydrogenase
RT and hydratase act as separate entities, as revealed by structure and
RT kinetics.";
RL Biochem. J. 435:771-781(2011).
CC -!- FUNCTION: Bifunctional enzyme acting on the peroxisomal beta-oxidation
CC pathway for fatty acids. {ECO:0000269|PubMed:21320074}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:32711, ChEBI:CHEBI:15378, ChEBI:CHEBI:57319,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726;
CC EC=1.1.1.n12; Evidence={ECO:0000269|PubMed:21320074};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:26526, ChEBI:CHEBI:15377, ChEBI:CHEBI:57319,
CC ChEBI:CHEBI:58856; EC=4.2.1.119;
CC Evidence={ECO:0000269|PubMed:21320074};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=85.3 uM for (2E)-butenoyl-CoA (at 22 degrees Celsius)
CC {ECO:0000269|PubMed:21320074};
CC KM=66.7 uM for (2E)-hexenoyl-CoA (at 22 degrees Celsius)
CC {ECO:0000269|PubMed:21320074};
CC KM=31.4 uM for (2E)-decenoyl-CoA (at 22 degrees Celsius)
CC {ECO:0000269|PubMed:21320074};
CC Vmax=1.07 umol/min/mg enzyme with (2E)-butenoyl-CoA (at 22 degrees
CC Celsius) {ECO:0000269|PubMed:21320074};
CC Vmax=15.0 umol/min/mg enzyme with (2E)-hexenoyl-CoA (at 22 degrees
CC Celsius) {ECO:0000269|PubMed:21320074};
CC Vmax=31.4 umol/min/mg enzyme with (2E)-decenoyl-CoA (at 22 degrees
CC Celsius) {ECO:0000269|PubMed:21320074};
CC Note=Catalytic efficiency is similar using full-length protein or the
CC individual (3R)-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase
CC 2 domains in a 1:1 mixture. {ECO:0000269|PubMed:21320074};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000250|UniProtKB:P51659}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:21320074}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:P51659}.
CC -!- MISCELLANEOUS: Complements functionally the S.cerevisiae peroxisomal
CC MFE-2 in vivo.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000255}.
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DR EMBL; AE014298; AAF48572.1; -; Genomic_DNA.
DR EMBL; AY051493; AAK92917.1; -; mRNA.
DR RefSeq; NP_001285318.1; NM_001298389.1.
DR RefSeq; NP_573109.1; NM_132881.3.
DR PDB; 3OML; X-ray; 2.15 A; A=1-598.
DR PDBsum; 3OML; -.
DR AlphaFoldDB; Q9VXJ0; -.
DR SASBDB; Q9VXJ0; -.
DR SMR; Q9VXJ0; -.
DR BioGRID; 58924; 11.
DR IntAct; Q9VXJ0; 5.
DR MINT; Q9VXJ0; -.
DR STRING; 7227.FBpp0073988; -.
DR PaxDb; Q9VXJ0; -.
DR PRIDE; Q9VXJ0; -.
DR DNASU; 32582; -.
DR EnsemblMetazoa; FBtr0074209; FBpp0073988; FBgn0030731.
DR EnsemblMetazoa; FBtr0340442; FBpp0309384; FBgn0030731.
DR GeneID; 32582; -.
DR KEGG; dme:Dmel_CG3415; -.
DR UCSC; CG3415-RA; d. melanogaster.
DR CTD; 32582; -.
DR FlyBase; FBgn0030731; Mfe2.
DR VEuPathDB; VectorBase:FBgn0030731; -.
DR eggNOG; KOG1206; Eukaryota.
DR HOGENOM; CLU_010194_18_4_1; -.
DR InParanoid; Q9VXJ0; -.
DR OMA; LITEMWK; -.
DR OrthoDB; 1120431at2759; -.
DR PhylomeDB; Q9VXJ0; -.
DR Reactome; R-DME-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-DME-2046106; alpha-linolenic acid (ALA) metabolism.
DR Reactome; R-DME-389887; Beta-oxidation of pristanoyl-CoA.
DR Reactome; R-DME-390247; Beta-oxidation of very long chain fatty acids.
DR Reactome; R-DME-9033241; Peroxisomal protein import.
DR SignaLink; Q9VXJ0; -.
DR UniPathway; UPA00659; -.
DR BioGRID-ORCS; 32582; 0 hits in 1 CRISPR screen.
DR EvolutionaryTrace; Q9VXJ0; -.
DR GenomeRNAi; 32582; -.
DR PRO; PR:Q9VXJ0; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0030731; Expressed in crop (Drosophila) and 24 other tissues.
DR ExpressionAtlas; Q9VXJ0; baseline and differential.
DR Genevisible; Q9VXJ0; DM.
DR GO; GO:0005777; C:peroxisome; ISS:FlyBase.
DR GO; GO:0106386; F:(3R)-hydroxyacyl-CoA dehydrogenase (NAD) activity; IEA:RHEA.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; ISS:FlyBase.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; ISS:FlyBase.
DR GO; GO:0080023; F:3R-hydroxyacyl-CoA dehydratase activity; IDA:FlyBase.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; IDA:FlyBase.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:FlyBase.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central.
DR GO; GO:0033540; P:fatty acid beta-oxidation using acyl-CoA oxidase; IC:FlyBase.
DR DisProt; DP02662; -.
DR InterPro; IPR029069; HotDog_dom_sf.
DR InterPro; IPR002539; MaoC-like_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR Pfam; PF01575; MaoC_dehydratas; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF54637; SSF54637; 2.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Fatty acid metabolism; Lipid metabolism; Lyase;
KW Multifunctional enzyme; NAD; Oxidoreductase; Peroxisome;
KW Reference proteome.
FT CHAIN 1..598
FT /note="Peroxisomal multifunctional enzyme type 2"
FT /id="PRO_0000416935"
FT DOMAIN 469..586
FT /note="MaoC-like"
FT /evidence="ECO:0000255"
FT REGION 1..309
FT /note="(3R)-hydroxyacyl-CoA dehydrogenase"
FT /evidence="ECO:0000269|PubMed:21320074"
FT REGION 310..598
FT /note="Enoyl-CoA hydratase 2"
FT /evidence="ECO:0000269|PubMed:21320074"
FT MOTIF 596..598
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 167
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P51659,
FT ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 16..40
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P51659"
FT BINDING 24
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P51659"
FT BINDING 43
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P51659"
FT BINDING 78..79
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P51659"
FT BINDING 102
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P51659"
FT BINDING 154
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51659"
FT BINDING 167..171
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P51659"
FT BINDING 199..202
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P51659"
FT BINDING 390..391
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT /evidence="ECO:0000250|UniProtKB:P22414"
FT BINDING 419
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT /evidence="ECO:0000250|UniProtKB:P22414"
FT BINDING 496..501
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT /evidence="ECO:0000250|UniProtKB:P22414"
FT BINDING 519
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT /evidence="ECO:0000250|UniProtKB:P22414"
FT BINDING 549
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT /evidence="ECO:0000250|UniProtKB:P22414"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:3OML"
FT TURN 18..21
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 23..34
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 58..67
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 82..86
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 116..142
FT /evidence="ECO:0007829|PDB:3OML"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 155..159
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 165..185
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 190..197
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 210..213
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 218..220
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 222..227
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 239..243
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 270..275
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 277..280
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 292..307
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 314..320
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 322..331
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 339..341
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 342..345
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 356..360
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 361..369
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 389..397
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 403..418
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 423..432
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 438..448
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 476..482
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 487..491
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 492..494
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 499..501
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 504..509
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 519..534
FT /evidence="ECO:0007829|PDB:3OML"
FT HELIX 539..541
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 542..549
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 558..566
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 569..576
FT /evidence="ECO:0007829|PDB:3OML"
FT TURN 577..579
FT /evidence="ECO:0007829|PDB:3OML"
FT STRAND 582..591
FT /evidence="ECO:0007829|PDB:3OML"
SQ SEQUENCE 598 AA; 64073 MW; 24205DE78964319A CRC64;
MSSSDGKLRY DGRVAVVTGA GAGLGREYAL LFAERGAKVV VNDLGGTHSG DGASQRAADI
VVDEIRKAGG EAVADYNSVI DGAKVIETAI KAFGRVDILV NNAGILRDRS LVKTSEQDWN
LVNDVHLKGS FKCTQAAFPY MKKQNYGRII MTSSNSGIYG NFGQVNYTAA KMGLIGLANT
VAIEGARNNV LCNVIVPTAA SRMTEGILPD ILFNELKPKL IAPVVAYLCH ESCEDNGSYI
ESAAGWATKL HMVRGKGAVL RPSLDDPVTI EYVKDVWSNV TDMSKAKHLG AIAEASGTLL
EVLEKLKEGG GDAIEDAFEF NSKELITYAL GIGASVKNAK DMRFLYENDA DFAAIPTFFV
LPGLLLQMST DKLLSKALPN SQVDFSNILH GEQYLEIVDD LPTSGTLLTN GKVFDVMDKG
SGAVVVTNSE SFDESGRLLV RNQSTTFIVG AGKFGGKKDP IAGVVPLQPA PNRQPDATVQ
YTTSEDQAAL YRLSGDKNPL HIDPQMALLA GFKTPILHGL CTLGFSVRAV LAQFADNNPA
LFKAVKVRFS GPVIPGQTLR VDLWKQGTRI NFRTVVVETG KEVISGAYVD LKSSQAKL
